title: The influence of severe hypoalbuminemia on the half-life of vancomycin in elderly patients with methicillin-resistant Staphylococcus aureus hospital-acquired pneumonia.
abstract: BACKGROUND
  Vancomycin (VCM) treatment outcomes depend on the characteristics of the patient, and it is well known that hypoalbuminemia is a risk factor for poor treatment outcomes, as reported in a previous study. However, the reason that severe hypoalbuminemia has an influence on the treatment outcome of VCM remains unknown.
  
  
  OBJECTIVE
  To elucidate the association between severe hypoalbuminemia and VCM treatment outcomes, we examined pharmacokinetic/pharmacodynamic (PK/PD) parameters in elderly patients with severe hypoalbuminemia.
  
  
  METHODS
  We conducted a retrospective observational study of 94 patients with methicillin-resistant Staphylococcus aureus (MRSA) hospital-acquired pneumonia who had been treated with VCM between January 2006 and December 2012. The 94 patients were divided into severe hypoalbuminemia and non-severe hypoalbuminemia groups. The PK/PD parameters and treatment outcomes of VCM were compared between the two groups.
  
  
  RESULTS
  The half-life of VCM in the severe hypoalbuminemia group was significantly longer than in the non-severe hypoalbuminemia group (33.2 + 5.4 vs 24.9 + 1.6; P = 0.049). Area under the concentration curve (AUC)/minimum inhibitory concentration (MIC) values of 250-450 and >450 μg × h/mL were significantly associated with 28-day mortality in the severe hypoalbuminemia group (P < 0.001), whereas AUC/MIC values of <250 μg × h/mL were not associated. We also detected a significant difference in the increased percentage of nephrotoxicity in the severe hypoalbuminemia group (6 of 23 patients [26%]) compared with the non-severe hypoalbuminemia group (6 of 71 patients [8%]; P < 0.001).
  
  
  CONCLUSIONS
  These findings indicate that severe hypoalbuminemia influences the half-life of VCM and treatment outcomes in elderly patients (≥75 years of age). To establish a more effective and safer treatment protocol, the issue of malnutrition in elderly patients needs to be addressed and improved.
authors.affiliation: Department of Analytical Pharmacology, Meijo University Graduate School of Pharmacy, Nagoya, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Mizuno
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Mizokami
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Fukami
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ito
authors.forename: Masataka
authors.initials: M
authors.lastname: Shibasaki
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nagamatsu
authors.forename: Katsunori
authors.initials: K
authors.lastname: Furuta
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003428:Cross Infection / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D034141:Hypoalbuminemia / Q000150:complications*; D007564:Japan / Q000453:epidemiology; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014640:Vancomycin / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: elderly patients; methicillin-resistant Staphylococcus aureus; pharmacodynamics; pharmacokinetics; severe hypoalbuminemia; vancomycin